Which plasma pTau217 assay should I use in clinical practice? Pandora’s box demystified

Brain, Journal Year: 2025, Volume and Issue: 148(2), P. 354 - 356

Published: Jan. 11, 2025

This scientific commentary refers to ‘A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests’ by Warmenhoven et al. (https://doi.org/10.1093/brain/awae346) and ‘Plasma p-tau217 in Alzheimer’s disease: Lumipulse ALZpath SIMOA comparison’ Pilotto (https://doi.org/10.1093/brain/awae368).

Language: Английский

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Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Global implementation of blood tests for Alzheimer’s disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, n = 337), Gothenburg 165), Barcelona (Spain, 487) Brescia (Italy, 230), a primary cohort Sweden ( 548). Plasma p-tau217 was primarily measured fully automated, commercially available, Lumipulse immunoassay. outcome AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. detected areas under receiver operating characteristic curves 0.93–0.96. care, accuracies were 89–91%, positive predictive values 89–95% negative 77–90%. accuracy 85%, 82% 88%. Accuracy lower aged ≥80 years (83%), but unaffected chronic kidney disease, diabetes, sex, APOE genotype or stage. Using two-cutoff approach, increased to 92–94% excluding 12–17% intermediate results. p-tau217:Aβ42 ratio did not improve reduced test results (≤10%). Compared high-performing mass-spectrometry-based assay percentage p-tau217, comparable care. However, had higher age. conclusion, this automated demonstrates high identifying pathology. A approach might necessary optimize performance across diverse settings subpopulations.

Language: Английский

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Differences in Alzheimer's disease blood biomarker stability: Implications for the use of tau/amyloid ratios

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

We compare the stability of phosphorylated tau (p-tau)217, amyloid beta (Aβ)42, Aβ40, Aβ42/40, and p-tau217/Aβ42 at different storage temperatures. Ten ethylenediaminetetraacetic acid-plasma sample aliquots stored frozen, refrigerated, ambient temperatures were tested various timepoints up to 30 days. The mean percent change from baseline was calculated. Aβ42 Aβ40 concentrations decreased by >15% after 6 hours temperature 24 while p-tau217 remained stable over 72 with < 10% deviation either temperature. Aβ42/40 ratio relatively constant as each analyte concentration concurrently, deviated time. All biomarkers days frozen. Differences in may lead altered results if samples are not handled properly during pre-analytical testing phase. Ideally, should be frozen promptly sent laboratory Plasma assessed. P-tau217 stable, but started decreasing differences led falsely increased ratios. Increases > 15% seen or 4°C.

Language: Английский

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Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION Proteomic evaluation of plasma samples could accelerate the identification novel Alzheimer's disease (AD) biomarkers. We evaluated NUcleic acid Linked Immuno‐Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort. METHODS Plasma biomarkers were measured with NULISA Human Connectome Project, a predominantly preclinical biracial community cohort southwestern Pennsylvania. Selected additionally using Simoa and Quest immunoassays compared. RESULTS On NULISA, phosphorylated tau (p‐tau217, p‐tau231, p‐tau181), glial fibrillary acidic protein (GFAP), microtubule‐associated (MAPT‐tau) showed top significant association amyloid beta (Aβ) positron emission tomography (PET) status, followed by neuroinflammation markers C‐C motif ligand 2 (CCL2), chitotriosidase 1 (CHIT1) interleukin‐8 (CXCL8), synaptic marker neurogranin (NRGN). Biomarkers associated cortical thickness included astrocytic chitinase‐3‐like (CHI3L1), cytokine CD40 (CD40LG), brain‐derived neurotrophic factor (BDNF), Aβ‐associated metalloprotein TIMP3 (tissue inhibitor 3), ficolin (FCN2). Furthermore, moderate to strong between‐platform correlations observed for various assays. DISCUSSION multiplexing advantage allowed concurrent assessment established Aβ pathology neurodegeneration. Highlights Classical next‐generation sequencing readout (NULISAseq) CNS panel concordance those immunoassay methods from Quanterix Quest, (GFAP) neurofilament light (NfL) exhibiting strongest correlation. NULISAseq analysis identified several strongly AD older adults. Notably, tau‐217 (p‐tau217), GFAP, p‐tau231 displayed pathology, whereas (BDNF) was demonstrate that biomarker levels be influenced age, sex, apolipoprotein E ( APOE ) genotype, self‐identified race. Specifically, NfL, surfactant D (SFTPD) age; CD63 S100 calcium‐binding B (S100B) race; synaptosomal‐associated 25 (SNAP25) genotype; serum A1 (SAA1) superoxide dismutase (SOD1) sex differences.

Language: Английский

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Advances in the Pathogenesis and Therapetic Strategies of Tau Proteins in Alzheimer’s Disease

Pharmacy Information, Journal Year: 2025, Volume and Issue: 14(02), P. 129 - 138

Published: Jan. 1, 2025

Language: Английский

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Analytical and clinical performance of eight Simoa® and Lumipulse® assays for automated measurement of plasma p-tau181 and p-tau217

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 19, 2024

Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed comprehensive method comparison study, followed by evaluation performance eight recent plasma p-tau immunoassays targeting different phosphorylation sites, fragments, and that are two distinct platforms. We enrolled cohort 40 patients with AD at stage dementia (AD-dem) characterized positive CSF A + T profile, control group cognitively healthy participants (Control), conduct for three p-tau181 five p-tau217 assays run on Simoa® HD-X™ or Lumipulse® G600II/G1200 Design compared differed regard to: (1) site targeted capture antibody (T181 T217), (2) epitope pan-tau detector (N-terminal mid-region). For each determined precision analytical sensitivity parameters used Passing-Bablok regression Bland-Altman plots pairwise assays. Subsequently, evaluated accuracy all discrimination between AD-dem Control groups. found strong, correlation measurements. Fixed and/or proportional bias was observed assay pairs pairs. While both levels were significantly increased vs. groups as assays, higher median concentration AD-dem/Control fold change AUC values (assays range: 3.72–6.74, 0.916–0.956) range 1.81–2.94, 0.829–0.909), independently platform used. No significant differences N-terminus mid-region. Although measurements enabled clinical groups, showed highest robustness, N-terminal mid-region, Considering disagreement absolute concentrations, stress need development certified reference material, harmonizing across

Language: Английский

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Targeted Proteomic Biomarker Profiling Using NULISA in a cohort enriched with risk for Alzheimer's Disease and Related Dementias

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Structured Abstract INTRODUCTION Targeted proteomic assays may be useful for diagnosing and staging Alzheimer’s disease related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning AD spectrum. METHODS Cross-sectional plasma (n=252) were analyzed using Alamar’s NULISAseq CNS panel. ROC analyses demonstrated NULISAseq-pTau217 accuracy detecting amyloid (A) tau (T) PET positivity. Differentially expressed proteins identified volcano plots. RESULTS accurately classified A/T status with AUCs 0.92/0.86. pTau217 was upregulated A+, T+, impaired groups log2-fold changes 1.21, 0.57 4.63, respectively, compared to A-. Interestingly, pTDP43-409 also group correlated declining hippocampal volume cognitive trajectories. DISCUSSION This study shows potential targeted proteomics characterizing brain pertinent ADRD. The promising findings require further replication.

Language: Английский

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Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum largely unexplored despite being preferred matrix many laboratories. To address this gap, we compared concentrations and diagnostic performances matched plasma samples using four research-use-only assays, including three from commercial sources i.e., Lumipulse, ALZpath, NULISA, one University Pittsburgh. Paired were processed same venipuncture collection assessed with following manufacturer-recommended procedures two research cohorts (N=84). Plasma levels varied across assays; Pittsburgh, NULISA methods showed significantly lower (p<0.0001), while Lumipulse higher or non-significant differences serum. Yet, strong correlations (rho >0.8) observed between pairs. Both demonstrated classification accuracies to differentiate AD normal controls, high AUC (up 0.963) all methods. The exception was Pittsburgh assay, where had superior than (plasma: 0.912, serum: 0.844). rest equivalent both matrices. Serum performs equivalently as assays. can therefore be used place assessment purposes.

Language: Английский

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